Maintenance of an adequate supply of oxygen to the body tissues is necessary for survival. Because the oxygen-carrying capacity of blood is governed by the concentration of erythrocytes in the blood, the appropriate regulation of erythropoiesis, the process by which red blood cells are produced, is critical.
Anemia is generally defined as a decrease in the number of red blood cells or reduced hemoglobin in the blood, and can be caused by decreased erythropoiesis. Anemias associated with aging, infectious disease, chronic renal failure, end-stage renal disease, renal transplantation, cancer, AIDS, antiviral therapy, chronic stress, chemotherapy, radiation therapy, bone marrow transplantation, and of genetic origin generally require therapies to induce erythroid differentiation, and therefore to increase red blood cell output. Currently, erythropoietin (Epo), a glycoprotein hormone that controls erythropoiesis, and its pharmacological derivatives are used to treat anemias such as anemia resulting from chronic kidney disease. However, many anemias are Epo-insensitive. In addition, in certain contexts, Epo treatment has been associated with undesirable side effects such as myocardial infarction, stroke, venous thromboembolism and tumor recurrence. What is needed are novel modes of stimulating erythropoiesis.